Effects of Yokukansankachimpihange on Memantine-induced Dizziness in Mice with Memory Impairment

Abstract

Memantine (Mem) is a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist used in the treatment of Alzheimer's disease. However, side effects, including dizziness, headache and confusion, have been reported. Therefore, although it reduces the symptoms of dementia, such as memory loss, its use is limited by side effects for patients at risk of injury. In the present study, we investigated the effects of the Japanese Kampo medicine yokukansankachimpihange (YKSCH) on Mem-induced dizziness in a mouse model of memory impairment. Mem (20 mg/kg B.W., p.o.) reduced the performance score during the beam balance test and walking time on a rotarod, confirming the disrupted sense of balance and motor coordination. In contrast, YKSCH (750 mg/kg B.W., p.o.) significantly suppressed this disruption of balance and motor coordination in mice. Moreover, YKSCH did not attenuate the ameliorative effects of Mem on learning and memory impairment in the Y-maze test or step-through passive avoidance task. Spatial learning and memory significantly recovered in the Mem-treated group and Mem plus YKSCH-treated group, suggesting no pharmacological interaction between Mem and YKSCH in mice. Therefore, YKSCH may be effective at alleviating the Mem-induced equilibrium disturbance in mice with memory impairment without reducing its memory disorder improvement effects. Our study may be useful for future studies on the combined use of Mem and YKSCH in the treatment of Alzheimer's disease.